Defining criteria for disease activity states in juvenile idiopathic arthritis: Table 1

What are the optimal JADAS cut-offs? Of late, the Juvenile Arthritis Disease Activity Score (JADAS) has gained increasing popularity for the measurement of the level of disease activity in patients with JIA. JADAS is a composite disease activity index that is made up by pooling four individual measures: physician’s global assessment of disease activity (PGA), parent’s/patient’s assessment of child’s well-being (PPGA), count of joints with active arthritis (assessed in 71, 27 or 10 joints, depending on the version) and ESR [1]. Recent studies have shown that the ESR can be replaced by the CRP value without altering the performance of the instrument [2]. In addition, a three-item version (so-called clinical JADAS, cJADAS), which excludes the acute phase reactant (and is more feasible for use in daily practice), was found to correlate closely with the original tool [3]. An important advance was the establishment of the cut-off values of JADAS that correspond to the main disease activity states of JIA [4–7]. In this issue of Rheumatology, Backström et al.. [8], adds to this data by presenting the cut-off values for inactive disease (ID), low disease activity (LDA) and moderate disease activity obtained in a sample of Finnish patients with non-systemic JIA. The establishment of criteria for identifying high and low levels of JIA activity is fundamental for interpreting the JADAS scores. Furthermore, it provides simple and intuitive reference values that can be used to monitor the course of the disease in an individual patient or to compare disease status across individual patients or patient groups. Categorization is also helpful to support decisions about entry into clinical trials as well as requirements for changes in therapies and to define therapeutic goals. Therefore, JADAS and its cut-offs constitute an easy and flexible method to guide therapeutic interventions aimed at pursuing tight disease control. Backström et al.. [8] focused on the JADAS10 and cJADAS10 and assigned patients to the oligoarticular or polyarticular disease groups based on the history of arthritis in ⩽4 or >4 joints, respectively. The Wallace et al.. [9] and Beukelman et al.. [10] definitions were chosen as external criteria against which to determine the optimal cut-offs for the states ID, LDA, moderate disease activity and high disease activity (HDA). The cut-offs obtained by Backström et al.. [8] are slightly different from those previously found by us in a cohort of Italian patients with JIA [4–6] (Table 1), particularly in the oligoarthritis subgroup. These discrepancies can be partially explained by differences in the study samples and in the methodology used to calculate the cut-offs. Comparison of JADAS cut-offs between the studies of Backström et al. [8] and Consolaro et al. [4–6] Comparison of JADAS cut-offs between the studies of Backström et al. [8] and Consolaro et al. [4–6] In the Finnish cohort, the parents and patients provided a higher global assessment than the physicians in 66% of visits. As a result, as many as 45% of patients with ID by the Wallace et al. criteria (which do not include the PPGA) had higher JADAS cut-off values due to high PPGA without having clinical evidence of active arthritis. As pointed out by the authors, these findings are in contrast with our previous observation of Italian patients that the PGA tended to be higher than the PPGA and that the PPGA incongruously inflated the score in the JADAS in only 2.6% of visits [6]. The observed discordance shows that parents’ and children’s perceptions of disease activity and burden may vary across ethnic and cultural environments. Further studies are needed to investigate whether this phenomenon is a limitation of using the PPGA in the JADAS. However, we believe that it important to integrate the parents’ and children’s perspective into clinical assessment as it may help with the physician’s choices and improve adherence to treatment. Backström et al. [8] could not calculate the cut-offs for HDA because only 2 of their 509 patients (0.4%) met the Beukelman et al. [10] criteria for HDA. This shortcoming can be partly due to their use of each patient’s most recent visit in the analyses. As shown by the low median values of the individual components of the JADAS in Table 2 of their paper, most patients had a well-controlled disease at the time of the study visit. Thus, the study sample was better suited to calculating the cut-offs for ID and LDA, rather than for HDA. Another possible explanation could be the choice of the Beukelman et al. [10] criteria to define HDA. Although these criteria are based on objective parameters, they are not evidence-based, but merely based on expert consensus. In addition, they are quite strict. In our series, only around 20% of patients had HDA by the Beukelman et al. [10] criteria at the start of etanercept therapy (A. Consolaro et al., unpublished observation). We do not agree with the authors’ contention that a definition of HDA based on clinician’s decisions to start drug treatment may be ambiguous. In our view, this approach, which was used in our previous analyses [5, 6] and in the study of Bulatovic et al. [7], is more appropriate as it reflects clinical practice and confers greater face validity to the cut-offs. Alternative methods along the same lines are represented by a consensus definition based on the assessment of patient profiles or a judgemental approach (i.e. explicitly asking doctors their opinion on what they would consider HDA). We recognize, however, that a potential limitation to these approaches is that clinical perceptions and treatment choices vary between physicians from different regions and according to their particular expertise. A consensus effort among paediatric rheumatologists is required to establish the best way of defining HDA in JIA. Because Backström et al. [8] evaluated only patients with non-systemic JIA, their work does not fill the gap of the lack of a JADAS version specific for the systemic subtype of JIA. Owing to the peculiarity and frequent prominence of extra-articular symptoms in patients with this disease, a modification of the tool that incorporates the assessment of systemic manifestations may be required. In conclusion, the study of Backström et al. [8] is commendable and timely, and represents a further step towards the incorporation of the JADAS and its cut-offs in paediatric rheumatology care and clinical trials. Additional studies involving patients of different ethnicity are needed to define optimal JADAS criteria for disease activity states that could be uniformly applied in JIA patient populations seen worldwide. Future research agenda should call for a collaborative study aimed at developing a JADAS version for systemic JIA. Funding: No specific funding was received from any funding bodies in the public, commercial or not-for-profit sectors to carry out the work described in this manuscript. Disclosure statement: The authors have declared no conflicts of interest.